Skin substitute and wound dressing with added anti-scar compound

ABSTRACT

An improved skin substitute is presented comprised of a silicone layer backed up with a woven nylon fabric layer, the silicone layer possessing a regular pattern of slits that permit the porosity of the skin substitute to be adjusted by clinicians by means of applying tension to the skin substitute that differentially opens the slits. A variety of therapeutic substances can be applied to the skin substitute to promote healing, including aloe and other medicinal preparations. A layer of water soluble or water insoluble anti-scar compound is also present, the preferred compound being salinomycin.

RELATED APPLICATIONS

This application is a Continuation-In-Part of U.S. patent applicationSer. No. 13/897,430 filed 19 May 2013.

FIELD OF THE INVENTION

This invention relates to dressings and bandages for acute and chronicwounds.

BACKGROUND OF THE INVENTION

Wound management involves removal of all non-viable tissue at the woundsite, preserving the remaining viable tissue, and providing a moist butnot wet environment. An example of successful burn wound dressing isBiobrane, granted U.S. Pat. No. 4,725,279. In 1979 Biobrane wasinitially studied by American Burn Surgeons; it is still popularworld-wide.

In 2007 new art was introduced by this inventor with AWBAT and then withAWBAT Plus, granted U.S. Pat. No. 7,815,931 and covered by severalcopending patent applications. The key to the success of these productswas better porosity in the dressing.

Recently, this inventor has revisited the art of dressing design. Thepresent invention allows passage of fluid adjacent to the wound throughthe primary dressing into a secondary absorbent dressing as well asimproving the kinetics of uninterrupted wound healing. Technology ofthis dressing has evolved into a new product which possesses all thecharacteristics and attributes known to be important for optimal woundhealing, as well as containing certain advances that result inminimization of wound desiccation and infection complication.

SUMMARY OF THE INVENTION

Wound sites have variable amounts of exudate/transudate/plasma present,from dry to weepy. The clinician must cleanly debride the wound, closeit and manage wound healing in a moist but not wet environment toachieve optimal results in both acute and chronic wounds.

The present invention provides a dressing that possesses all theproperties and attributes of an ideal skin substitute and, in addition,has ‘variable porosity’ controlled by the clinician from essentiallyzero porosity to what the wound requires. The present invention enablesthe clinician to move the fluid exuding from the wound through theprimary dressing into an absorbent secondary dressing without disturbingthe kinetics of healing or causing pain to the patient.

The present invention is cost effective at every level. Patients gettheir wounds managed with minimal pain and optimal healing times. Thedressing is cost effective as the hospital needs to inventory only oneprimary dressing for acute wounds (burns) and one for chronic wounds;each has a two year shelf-life at room temperature.

The present invention is composed of one or two biological layerssprayed on in one or two separate operations. The first layer sprayedonto the nylon side of the “variable porosity” silicone membrane willbe: (1) a solution of pure Aloe (Aloesin, Immuno10, Qmatrix andLoesyn—each hydrophilic and hygroscopic); (2) a solution of pure Aloeand hypoallergenic USP Pharmaceutical Grade porcine gelatin; or (3) afine suspension of pure Aloe, gelatin and ECM (as fine insolubleparticles or hollow spheres in water—the latter possesses improvedhealing properties). In vitro, the Aloe component has been demonstratedto cause a variety of cells to attach and proliferate; as well asincrease synthesis of collagen and alpha smooth muscle actin. ECM may beadded to the biologicals described above and is a mixture from humanfibroblasts that is known to cause rapid cell proliferation and tissuegrowth. Previous wound dressings and skin substitutes, as taught in U.S.Pat. No. 7,815,931 contain gelatin, a pure Aloe component, chondroitin 4& 6 sulfate, and vitamin C & E. In contrast the current dressing willhave two layers of biologicals applied in separate spraying operationsas described above.

The first coat will contact the wound after the second coat ofhypoallergenic bovine spongiform encephalopathy (BSE)-free United StatesPharmaceutical (USP)-grade gelatin interacts with fibrin in the wound toachieve early adherence. The second coat of biologicals stimulates thehealing process during the interval where the dressing invention is incontact with the wound and is stable requiring 100 degree water for 30minutes to remove from the “variable porosity” silicone/nylon surface.

Water soluble or water insoluble anti-scar compound(s) can beincorporated into the 3D matrix of this variable porosity skinsubstitute. The preferred embodiment of the anti-scar compound issalinomycin, which can be incorporated in two ways—into the hydrophobicsolid silicone component of the skin substitute or into the watersoluble biological coating used to coat the 3D surface.

BRIEF DESCRIPTION OF THE FIGURES

FIG. 1. The embodiments of the invention, showing the slit openings

FIG. 2. The wale and course nature of the woven fabric

FIG. 3. An example of punctuate scarring

DETAILED DESCRIPTION

The present invention is similar in composition to earlier skinsubstitutes in that they each have a thin silicone component, thesilicone membrane selected in a thickness from 0.001″ to 0.005″, and anunderlying thin knitted nylon component. The present invention differsfrom its ancestors in that it has “variable porosity” controlled by theclinician; the pore size in the thin silicone will be essentially zero(with no stretch, in relaxed mode) to a higher porosity (proportional tothe stretch applied). See FIG. 1 for the optional stretch modes. Inaddition, the present invention differs in the composition of biologicalcoatings applied to both components and how these coatings interact withthe wound over time.

The pores of prior art skin substitutes/dressings are of a fixed size(Biobrane 1.2%; AWBAT and AWBAT Plus 5.5% and 7.5%) in the unstretchedopen position; the silicone is cured while the skin substitute pores areopen. Once cured the pores cannot close or be reduced in size; thiscauses wound desiccation and punctate scarring. As in FIG. 1, incontrast, the openings are made after the silicone component has beencured, and are in the shape of slits, not holes. The figure shows theskin substitute silicone layer up with the slits exposed.

The “wale” and “course” orientations of stitching of the knitted nyloncomponent of the invention are shown in FIG. 2. The preferred embodimentof the invention is shown in FIG. 1. In this embodiment, designed forburns, the slits 103 made in the silicone are approximately 0.250″ long101 with a space of 0.250″ between slits 102; parallel rows of slits are0.250″ apart. The parallel rows of slits are oriented such that theslits are parallel to the “wale” orientation of the Jersey stitchpattern of the knitted nylon component. The “wale” orientation hasmeasurably less elongation than the “course” orientation.

Because of the orientation of the slits, stretch along the axis of theslits is minimal and stretch perpendicular to the slit axes ismaximized. With no stretch of the silicone/nylon membrane the slitscannot be seen without magnification while observing from above andprovide essentially zero porosity.

The preferred embodiment is effective, particularly on partial thicknessburns where punctate scarring has been observed. In the preferredembodiment, with no stretch, the wound is protected by an essentiallycontinuous thin silicone membrane which minimizes wound desiccation andpunctate scarring. This enables the clinician to stretch the dressingparallel to the direction of the slits with minimal opening of theslits. This is parallel to the “wale” direction of the underlyingfabric. Fluids from the wound can still escape through the closed slitsand be absorbed into a secondary dressing, which can be removed andreplaced without interfering with the healing process or causing pain tothe patient.

The combination of a primary dressing that requires minimal changes anda secondary dressing that is easy to change and replace reduces woundmaintenance costs which benefits patient, staff and hospital. An exampleof punctate scarring is illustrated in FIG. 3; the figure shows the skinof a patient whose burn was covered with the ancestor AWBAT dressingwith a fixed porosity of at least 5.5%.

Chronic, slow healing wounds require similar treatment as burns in thatall necrotic tissue must be removed before closing the wound with aprimary dressing. In the chronic wound, exudate and other fluids areoften removed with negative pressure wound therapy (NPWT). A negativepressure above the wound or a positive pressure from the wound causesexudate and other wound fluids to pass through the primary dressing intoa secondary dressing. The primary dressings currently used during NPWTare: urethane foam, polyvinyl alcohol foam or cotton gauze; all requirefrequent dressing changes and infection complications have been reportedwhen these dressings are not changed frequently.

The present invention will have two layers of water-soluble biologicals;first a clotting outer layer containing hypoallergenic BSE free USPPharmaceutical grade gelatin. This layer contacts the wound first andstimulates initial adherence of the dressing to the cleanly debridedwound. The second layer of pure Aloe or Aloesin, pure Aloe and BSE freegelatin, or a mixture of pure Aloe, BSE free gelatin and ECM interactwith the wound to stimulate the rate of healing while adherent to thewound. The first layer is deposited directly on the nylon side of the“variable porosity” silicone/nylon surface and is stable, i.e. requires100 degree water for 30 minutes to remove from the “variable porosity”silicone/nylon surface.

Water soluble or water insoluble anti-scar compound(s) can beincorporated into the 3D matrix of this variable porosity skinsubstitute. The preferred embodiment of the anti-scar compound issalinomycin, which can be incorporated in two ways—into the hydrophobicsolid silicone component of the skin substitute or into the watersoluble biological coating used to coat the 3D surface. The structure ofsalinomycin is shown below.

In one embodiment, salinomycin is formulated in a topical compositioncomprising salinomycin and a carrier or excipient suitable for dermalapplication. The term “carrier or excipient” as used herein, refers to acarrier or excipient that is conventionally used in the art tofacilitate the storage, administration, and/or the biological activityof an active compound. A carrier may also reduce any undesirable sideeffects of the active compound. A suitable carrier is, for example,stable, e.g., incapable of reacting with other ingredients in theformulation. In one example, the carrier does not produce significantlocal or systemic adverse effect in recipients at the dosages andconcentrations employed for treatment. Such carriers and excipients aregenerally known in the art. Suitable carriers for this invention includethose conventionally used, e.g., water, saline, aqueous dextrose, andglycols are preferred liquid carriers, particularly (when isotonic) forsolutions. Suitable pharmaceutical carriers and excipients includestarch, cellulose, glucose, lactose, sucrose, gelatin, malt, rice,flour, chalk, silica gel, magnesium stearate, sodium stearate, glycerolmonostearate, sodium chloride, glycerol, propylene glycol, water,ethanol, and the like. Suitable carriers for topical application of acompound are known in the art and include, for example, methyl cellulose(e.g., 3% methylcellulose; Beck et al., Growth Factors, 3: 267, 1990),silver sulfadiazene cream (Schultz et al., Science, 235: 350, 1985),multilamellar lecithin liposomes (Brown et al., Ann Surg., 208: 788,1988) or hyaluronic acid (Curtsinger et al., Surg. Gynecol. Obstet.,168: 517, 1989). In some examples, the carrier can be a co-polymer, apaste or a hydrogel.

In some embodiments, the topical composition as described hereinaccording to any embodiment additionally comprises a compound thatenhances or facilitates uptake of salinomycin into and/or through skinof a subject. Suitable dermal permeation enhancers are, for example, alipid disrupting agent (LDA), a solubility enhancer, or a surfactant.

This is the preferred embodiment of the invention. The technology tocreate this invention is listed as the preferred embodiment of thisinvention, but other methods are possible and are within thecontemplation of this patent.

What is claimed is:
 1. A skin substitute, the skin substitute comprisedof two layers of material, the first layer of material, an upper layer,comprised of a silicone membrane, the second layer, a lower layer,comprised of a woven nylon fabric, the silicone membrane selected in athickness from 0.001″ to 0.005″, the upper layer possessing a pluralityof slits in its surface, said slits made after the two layers are joinedtogether, said slits in a pattern comprised of multiple rows of parallelslits, the lower layer woven in a regular pattern with a perpendicularwale and course orientation, the slits on the surface either followingthe wale direction of the lower layer or crossing the wale direction ofthe lower layer perpendicularly, said upper layer and said lower layertreated with a plurality of layers of medicinal or therapeuticsubstances applied to the two layers of the skin substitute, said lowerlayer also treated with a water soluble or water insoluble anti-scarcompound, said slits placed in said upper layer such that the skinsubstitute has essentially zero porosity with no stretching tensionplaced on it, the porosity of said skin substitute variable proportionalto the amount of stretching tension and the direction in which saidstretching tension is placed on the skin substitute, the direction ofstretching tension dependent on the orientation of said slits with thewale and course orientation of the woven nylon fabric, the skinsubstitute designed to place the woven nylon fabric side down on top ofa wound when in use, the skin substitute selected to be used incombination with an absorptive dressing placed above said skinsubstitute over the wound.
 2. The skin substitute of claim 1 where theplurality of slits are oriented in parallel with the wale orientation ofthe lower layer.
 3. The skin substitute of claim 2 where the pluralityof layers of medicinal and therapeutic substances are selected from thelist of hypoallergenic BSE free USP Pharmaceutical grade gelatin, purealoe, aloesin, ECM.
 4. The skin substitute of claim 1 where theanti-scar compound is comprised of salinomycin.
 5. The skin substituteof claim 4, wherein salinomycin is incorporated into (1) the siliconemembrane of the skin substitute or (2) the plurality of layers ofmedicinal or therapeutic substances.